ABSTRACT
Introduction: Measuring predicted post-operative diffusion capacity of the lung for carbon monoxide (ppoDLCO) is essential to determine patient operability and to stratify the risk of patients who are candidates for major lung cancer surgery. Studies that established surgical risk variables were based on open surgery series. The aim of our study was to analyze morbidity and mortality as a function of ppoDLCO and to compare its behavior in open and video-assisted thoracic surgery (VATS). Methods: We compared 90-day mortality and morbidity in patients undergoing open surgery versus VATS as a function of decline in ppoDLCO. Propensity score matching (using age, ASA, arterial vascular disease, BMI, gender, stage, ppoDLCO, and ppoFEV1) was applied to create comparable open surgery and VATS groups. Results: Of 2,530 patients with lung cancer and ppoDLCO values, a sample of 1,624 (812 per group) was obtained after score matching. The relative risk of mortality associated with thoracotomy in patients with ppoDLCO < 60 is 2.66 (p < 0.02) compared to VATS. The risk of thoracotomy in terms of overall and cardiac and respiratory morbidity is higher than that of VATS for almost all ppoDLCO values. Conclusions: Major resection by VATS shows lower morbidity and mortality in patients with the same ppoDLCO. A steady rise in the risk of mortality begins to occur at higher ppoDLCO values in thoracotomy (∼60) than in VATS (∼45). (AU)
Introducción: La medición de la capacidad de difusión del carbono monóxido postoperatoro (ppoDLCO) es esencial para la operabilidad del paciente y la estratificación del riesgo de los pacientes subsidiarios de una resección pulmonar mayor por cáncer. Los estudios que fijan los límites de riesgo quirúrgico se basan en series de cirugía abierta. El objetivo de nuestro trabajo es analizar la morbilidad y mortalidad en relación a la ppoDLCO y comparar su comportamiento en cirugía abierta y cirugía torácica videoasistida (VATS). Métodos: Comparación de la mortalidad a 90 días y la morbilidad en pacientes intervenidos por cirugía abierta frente a videoasistida en relación al descenso de la ppoDLCO. Emparejamiento por puntaje de propensión (variables: edad, ASA, vasculopatía arterial, IMC, sexo, estadio, ppoDLCO y ppoFEV1) para realizar grupos comparables entre abierta y VATS. Resultados: De 2.530 pacientes con cáncer de pulmón y medición de ppoDLCO, se obtiene tras el pareamiento por puntaje una muestra de 1.624 (812 por grupo). El riesgo relativo de mortalidad de la toracotomía para una ppoDLCO <60 es de 2,66 (p < 0,02) respecto a la videocirugía. Tanto para morbilidad total como para la cardíaca y respiratoria, el riesgo de la toracotomía es superior a la videocirugía para casi todos los valores de ppoDLCO. Conclusiones: La resección mayor por VATS muestra una morbimortalidad inferior para una misma ppoDLCO. El aumento continuo del riesgo de mortalidad empieza a darse en valores de ppoDLCO superiores en toracotomía (∼60) que en VATS (∼45). (AU)
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Lung Neoplasms , Thoracic Surgery, Video-Assisted/mortality , Spain , Pneumonectomy , Indicators of Morbidity and MortalityABSTRACT
INTRODUCTION: Measuring predicted post-operative diffusion capacity of the lung for carbon monoxide (ppoDLCO) is essential to determine patient operability and to stratify the risk of patients who are candidates for major lung cancer surgery. Studies that established surgical risk variables were based on open surgery series. The aim of our study was to analyze morbidity and mortality as a function of ppoDLCO and to compare its behavior in open and video-assisted thoracic surgery (VATS). METHODS: We compared 90-day mortality and morbidity in patients undergoing open surgery versus VATS as a function of decline in ppoDLCO. Propensity score matching (using age, ASA, arterial vascular disease, BMI, sexo, stage, ppoDLCO, and ppoFEV1) was applied to create comparable open surgery and VATS groups. RESULTS: Of 2,530 patients with lung cancer and ppoDLCO values, a sample of 1,624 (812 per group) was obtained after score matching. The relative risk of mortality associated with thoracotomy in patients with ppoDLCO<60 is 2.66 (P<.02) compared to VATS. The risk of thoracotomy in terms of overall and cardiac and respiratory morbidity is higher than that of VATS for almost all ppoDLCO values. CONCLUSIONS: Major resection by VATS shows lower morbidity and mortality in patients with the same ppoDLCO. A steady rise in the risk of mortality begins to occur at higher ppoDLCO values in thoracotomy (â¼60) than in VATS (â¼45).
ABSTRACT
INTRODUCTION: Measuring predicted post-operative diffusion capacity of the lung for carbon monoxide (ppoDLCO) is essential to determine patient operability and to stratify the risk of patients who are candidates for major lung cancer surgery. Studies that established surgical risk variables were based on open surgery series. The aim of our study was to analyze morbidity and mortality as a function of ppoDLCO and to compare its behavior in open and video-assisted thoracic surgery (VATS). METHODS: We compared 90-day mortality and morbidity in patients undergoing open surgery versus VATS as a function of decline in ppoDLCO. Propensity score matching (using age, ASA, arterial vascular disease, BMI, gender, stage, ppoDLCO, and ppoFEV1) was applied to create comparable open surgery and VATS groups. RESULTS: Of 2,530 patients with lung cancer and ppoDLCO values, a sample of 1,624 (812 per group) was obtained after score matching. The relative risk of mortality associated with thoracotomy in patients with ppoDLCOâ¯<â¯60 is 2.66 (pâ¯<â¯0.02) compared to VATS. The risk of thoracotomy in terms of overall and cardiac and respiratory morbidity is higher than that of VATS for almost all ppoDLCO values. CONCLUSIONS: Major resection by VATS shows lower morbidity and mortality in patients with the same ppoDLCO. A steady rise in the risk of mortality begins to occur at higher ppoDLCO values in thoracotomy (â¼60) than in VATS (â¼45).
Subject(s)
Lung Neoplasms , Thoracic Surgery, Video-Assisted , Humans , Morbidity , Pneumonectomy/adverse effects , Retrospective Studies , Thoracotomy , Treatment OutcomeABSTRACT
Irinotecan (CPT-11) is a drug used against a wide variety of tumors, which can cause severe toxicity, possibly leading to the delay or suspension of the cycle, with the consequent impact on the prognosis of survival. The main goal of this work is to predict the toxicities derived from CPT-11 using artificial intelligence methods. The data for this study is conformed of 53 cycles of FOLFIRINOX, corresponding to patients with metastatic colorectal cancer. Supported by several demographic data, blood markers and pharmacokinetic parameters resulting from a non-compartmental pharmacokinetic study of CPT-11 and its metabolites (SN-38 and SN-38-G), we use machine learning techniques to predict high degrees of different toxicities (leukopenia, neutropenia and diarrhea) in new patients. We predict high degree of leukopenia with an accuracy of 76%, neutropenia with 75% and diarrhea with 91%. Among other variables, this study shows that the areas under the curve of CPT-11, SN-38 and SN-38-G play a relevant role in the prediction of the studied toxicities. The presented models allow to predict the degree of toxicity for each cycle of treatment according to the particularities of each patient.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Diarrhea/chemically induced , Irinotecan/pharmacokinetics , Irinotecan/toxicity , Leukopenia/chemically induced , Machine Learning , Models, Biological , Neutropenia/chemically induced , Topoisomerase I Inhibitors/pharmacokinetics , Topoisomerase I Inhibitors/toxicity , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Camptothecin/analogs & derivatives , Camptothecin/metabolism , Colorectal Neoplasms/secondary , Female , Fluorouracil/administration & dosage , Forecasting , Glucuronates/metabolism , Humans , Irinotecan/administration & dosage , Irinotecan/adverse effects , Leucovorin/administration & dosage , Male , Middle Aged , Oxaliplatin/administration & dosage , Topoisomerase I Inhibitors/administration & dosage , Topoisomerase I Inhibitors/adverse effectsABSTRACT
PURPOSE: The present study was performed to demonstrate that small amounts of routine clinical data allow to generate valuable knowledge. Concretely, the aims of this research were to build a joint population pharmacokinetic model for capecitabine and three of its metabolites (5-DFUR, 5-FU and 5-FUH2) and to determine optimal sampling times for therapeutic drug monitoring. METHODS: We used data of 7 treatment cycles of capecitabine in patients with metastatic colorectal cancer. The population pharmacokinetic model was built as a multicompartmental model using NONMEM and was internally validated by visual predictive check. Optimal sampling times were estimated using PFIM 4.0 following D-optimality criterion. RESULTS: The final model was a multicompartmental model which represented the sequential transformations from capecitabine to its metabolites 5-DFUR, 5-FU and 5-FUH2 and was correctly validated. The optimal sampling times were 0.546, 0.892, 1.562, 4.736 and 8 hours after the administration of the drug. For its correct implementation in clinical practice, the values were rounded to 0.5, 1, 1.5, 5 and 8 hours after the administration of the drug. CONCLUSIONS: Capecitabine, 5-DFUR, 5-FU and 5-FUH2 can be correctly described by the joint multicompartmental model presented in this work. The aforementioned times are optimal to maximize the information of samples. Useful knowledge can be obtained for clinical practice from small databases.
Subject(s)
Antimetabolites, Antineoplastic/pharmacokinetics , Capecitabine/pharmacokinetics , Models, Biological , Adult , Aged , Antimetabolites, Antineoplastic/blood , Capecitabine/blood , Colorectal Neoplasms/blood , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Data Mining , Fluorouracil/blood , Humans , Middle Aged , Time FactorsABSTRACT
PURPOSE: Irinotecan (CPT-11) is a drug used against a wide range of tumor types. The individualized dosing of CPT-11 is essential to ensure optimal pharmacotherapy in cancer patients, given the wide interindividual pharmacokinetic variability of this drug and its active metabolite SN-38. Moreover, the reabsorption from SN-38-G to SN-38, by enterohepatic recirculation, is critical due to its influence in the treatment tolerance. The aim of this research was to build a joint population pharmacokinetic model for CPT-11 and its metabolites (SN-38, and its glucuronide, SN-38-G) that enabled an individualized posology adjustment. METHODS: We used data of 53 treatment cycles of FOLFIRINOX scheme corresponding to 20 patients with metastatic colorectal cancer. In order to build the population pharmacokinetic model, we implemented parametric and non-parametric methods using the Pmetrics library package for R. We also built multivariate regression models to predict the area under the curve and the maximum concentration using basal covariates. RESULTS: The final model was a multicompartmental model which represented the transformations from CPT-11 to its active metabolite SN-38 and from SN-38 to inactive SN-38-G. Besides, the model also represented the extensive elimination of SN-38-G and the reconversion of the remaining SN-38-G to SN-38 by enterohepatic recirculation. We carried out internal validation with 1000 simulations. The regression models predicted the PK parameters with R squared adjusted up to 0.9499. CONCLUSION: CPT-11, SN-38, and SN-38-G can be correctly described by the multicompartmental model presented in this work. As far as we know, it is the first time that a joint model for CPT-11, SN-38, and SN-38-G that includes the process of reconversion from SN-38-G to SN-38 is characterized.
